Study of TNF-Antagonism in Metabolic Syndrome

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00409318
First received: December 7, 2006
Last updated: May 23, 2008
Last verified: May 2008
  Purpose

This study investigates whether blockade of TNF will result in reduced inflammatory indices in patients with the metabolic syndrome


Condition Intervention
Metabolic Syndrome
Drug: Etanercept
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of TNF-Alpha Antagonism in Patients With the Metabolic Syndrome (I)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • CRP [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin resistance [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Muscle adiposity [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • High molecular weight adiponectin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • resistin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • leptin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • TNF-R1 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • TNF-R2 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • weight [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • WBC [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Lipids [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • IL-6 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Fibrinogen [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • adiponectin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: April 2004
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Etanercept
Drug: Etanercept
50 mg SC q week
Other Name: Enbrel
Placebo Comparator: 2
Placebo
Drug: Placebo
SC q week
Other Name: placebo

Detailed Description:

Metabolic syndrome is an increasingly prevalent disorder associated with elevated risks of type II DM (diabetes mellitus) and cardiovascular morbidity and mortality. A subclinical inflammatory state is thought to contribute to the pathophysiology of metabolic syndrome, insulin resistance, and coronary artery disease (CAD). TNF-alpha is an inflammatory cytokine that is increased in a spectrum of inflammatory diseases as well as in insulin resistance. TNF-alpha antagonists are clinically effective in the inflammation of arthritides, but have not been examined in the metabolic syndrome population. Moreover, data suggests that adiponectin, a recently discovered adipocytokine that may protect against the development of insulin resistance and atherosclerosis, may be downregulated by TNF-alpha. We propose a study in which we administer etanercept, a TNF-alpha receptor fusion protein, to subjects with metabolic syndrome to examine its effect on inflammatory markers,CRP, adiponectin and insulin resistance. This would be the first study to investigate the anti-inflammatory properties and insulin sensitizing potential of TNF-alpha blockade on the growing population with metabolic syndrome.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion Criteria based on a modified WHO definition of metabolic syndrome

  1. Hyperinsulinemia in the upper quartile of the non-diabetic population defined as >= 10 mU/mL (Framingham Data, oral communication,James Meigs, MD) or fasting glucose 110-126 mg/dL

    Plus two of the following:

  2. Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women or BMI > 30 kg/m2
  3. Dyslipidemia including serum triglycerides ³ 150 mg/dl or serum HDL < 0.9 mmol/L for men (35 mg/dL) and < 1.0 mmol/L (39mg/dL) for women
  4. Hypertension defined as blood pressure >= 140/90 or on medication

Exclusion Criteria:

  1. Positive PPD (³ 5mm induration) on screening
  2. Current Infection
  3. Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months
  4. Reception of live vaccine within 1 week of recruitment
  5. History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.
  6. History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers who will be eligible)
  7. History of organ transplantation
  8. History of CNS demyelinating disorder or any first degree relative with multiple sclerosis
  9. History of CHF classes I-IV
  10. Current use of insulin, any oral anti-hyperglycemic agents, pentoxyfylline, beta-agonists
  11. Current use of fibrate or niacin
  12. Initiation of statin therapy within prior 6 weeks or expecting a change in statin dose over the upcoming 3 months
  13. Hemoglobin < 11 g/dl
  14. Positive pregnancy test
  15. Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (IUD, condoms, diaphragms) or abstinence
  16. Patients with known autoimmune or inflammatory conditions (excluding patients with stable, treated hypothyroidism)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00409318

Locations
United States, Massachusetts
MGH
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Amgen
Investigators
Principal Investigator: Steven K Grinspoon MGH
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven Grinspoon, M.D., MGH
ClinicalTrials.gov Identifier: NCT00409318     History of Changes
Other Study ID Numbers: 2003-P-001699
Study First Received: December 7, 2006
Last Updated: May 23, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Inflammation
Visceral adiposity
TNF
CRP
Adiponectin
Insulin resistance
metabolic syndrome

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014